A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness

Abstract Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to...

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Autores principales:	John Lai, Leire Moya, Jiyuan An, Andrea Hoffman, Srilakshmi Srinivasan, Janaththani Panchadsaram, Carina Walpole, Joanna L. Perry-Keene, Suzanne Chambers, Australian Prostate Cancer BioResource, Melanie L. Lehman, Colleen C. Nelson, Judith A. Clements, Jyotsna Batra
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d9e5e6634f54987ae535d2c9dbf9217
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spelling	oai:doaj.org-article:5d9e5e6634f54987ae535d2c9dbf92172021-12-02T15:06:22ZA microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness10.1038/s41598-017-16700-y2045-2322https://doaj.org/article/5d9e5e6634f54987ae535d2c9dbf92172017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16700-yhttps://doaj.org/toc/2045-2322Abstract Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to identify polymorphic STRs that are readily expressed in these cells. Most of the expressed STRs in the clinical samples mapped to intronic and intergenic DNA. Our analysis indicated that three of these STRs (TAAA-ACTG2, TTTTG-TRIB1, and TG-PCA3) are polymorphic and differentially expressed in prostate tumors compared to adjacent non-malignant cells. TG-PCA3 STR expression was repressed by the anti-androgen drug enzalutamide in prostate cancer cells. Genetic analysis of prostate cancer patients and healthy controls (N > 2,000) showed a significant association of the most common 11 repeat allele of TG-PCA3 STR with prostate cancer risk (OR = 1.49; 95% CI 1.11–1.99; P = 0.008). A significant association was also observed with aggressive disease (OR = 2.00; 95% CI 1.06–3.76; P = 0.031) and high mortality rates (HR = 3.0; 95% CI 1.03–8.77; P = 0.045). We propose that TG-PCA3 STR has both diagnostic and prognostic potential for prostate cancer. We provided a proof of concept to be applied to other RNA sequencing datasets to identify disease-associated STRs for future clinical exploratory studies.John LaiLeire MoyaJiyuan AnAndrea HoffmanSrilakshmi SrinivasanJanaththani PanchadsaramCarina WalpoleJoanna L. Perry-KeeneSuzanne ChambersAustralian Prostate Cancer BioResourceMelanie L. LehmanColleen C. NelsonJudith A. ClementsJyotsna BatraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John Lai Leire Moya Jiyuan An Andrea Hoffman Srilakshmi Srinivasan Janaththani Panchadsaram Carina Walpole Joanna L. Perry-Keene Suzanne Chambers Australian Prostate Cancer BioResource Melanie L. Lehman Colleen C. Nelson Judith A. Clements Jyotsna Batra A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
description	Abstract Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to identify polymorphic STRs that are readily expressed in these cells. Most of the expressed STRs in the clinical samples mapped to intronic and intergenic DNA. Our analysis indicated that three of these STRs (TAAA-ACTG2, TTTTG-TRIB1, and TG-PCA3) are polymorphic and differentially expressed in prostate tumors compared to adjacent non-malignant cells. TG-PCA3 STR expression was repressed by the anti-androgen drug enzalutamide in prostate cancer cells. Genetic analysis of prostate cancer patients and healthy controls (N > 2,000) showed a significant association of the most common 11 repeat allele of TG-PCA3 STR with prostate cancer risk (OR = 1.49; 95% CI 1.11–1.99; P = 0.008). A significant association was also observed with aggressive disease (OR = 2.00; 95% CI 1.06–3.76; P = 0.031) and high mortality rates (HR = 3.0; 95% CI 1.03–8.77; P = 0.045). We propose that TG-PCA3 STR has both diagnostic and prognostic potential for prostate cancer. We provided a proof of concept to be applied to other RNA sequencing datasets to identify disease-associated STRs for future clinical exploratory studies.
format	article
author	John Lai Leire Moya Jiyuan An Andrea Hoffman Srilakshmi Srinivasan Janaththani Panchadsaram Carina Walpole Joanna L. Perry-Keene Suzanne Chambers Australian Prostate Cancer BioResource Melanie L. Lehman Colleen C. Nelson Judith A. Clements Jyotsna Batra
author_facet	John Lai Leire Moya Jiyuan An Andrea Hoffman Srilakshmi Srinivasan Janaththani Panchadsaram Carina Walpole Joanna L. Perry-Keene Suzanne Chambers Australian Prostate Cancer BioResource Melanie L. Lehman Colleen C. Nelson Judith A. Clements Jyotsna Batra
author_sort	John Lai
title	A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
title_short	A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
title_full	A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
title_fullStr	A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
title_full_unstemmed	A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness
title_sort	microsatellite repeat in pca3 long non-coding rna is associated with prostate cancer risk and aggressiveness
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5d9e5e6634f54987ae535d2c9dbf9217
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A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness

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